Suppression of HIV Type 1 Replication by a Dominant-Negative Ets-1 Mutant

Activity of the distal region of the human immunodeficiency virus (HIV-1) long terminal repeat (LTR), which contains binding sites for the Ets-1 and USF-1 proteins, is integral for HIV-1 replication. The Ets-1 and USF-1 proteins play a critical role in the activity of the HIV-1 LTR distal enhancer region, as indicated by the potent dominant negative effect of a mutant Ets-1 lacking trans-activation domains on the transcriptional activity of the LTR. To determine the biological relevance of the Ets-1 and USF-1 proteins in HIV-1 replication, we examined the effect of expression of the dominant-negative mutant of Ets-1 (dnEts-1) on HIV-1 infection of T cells. We demonstrated that expression of dnEts markedly suppressed HIV-1 infection of a T cell line. This finding indicates that formation of a transcriptionaly active USF-1/Ets-1 complex is important in the productive infection of cells by HIV-1, and suggests that inhibition of the interaction between USF-1 and Ets-1 with the HIV-1 LTR may provide a new target for anti-HIV-1 gene therapy.